CStone’s CS2009 shows promising anti-tumor activity in phase 1 trial

CStone Pharmaceuticals announced encouraging preliminary phase 1 data for CS2009, a PD-1/VEGF/CTLA-4 trispecific antibody, at the 2025 European Society for Medical Oncology (ESMO) annual congress. The dose escalation phase was completed without any dose-limiting toxicity (DLT), and the maximum tolerated dose (MTD) was not reached. Only one treatment-emergent adverse event led to permanent drug discontinuation (1.4% incidence), and no grade 4 or 5 treatment-related adverse events were observed. The incidence of grade ≥3 treatment-related adverse events was 13.9%.

Anti-tumor activity was observed across all dose levels in 49 evaluable patients with advanced solid tumors, resulting in an overall response rate (ORR) of 12.2% and a disease control rate (DCR) of 71.4%. Updated data beyond the poster cutoff showed a further improvement in ORR to 14.3%. Higher ORR (25.0%) was noted at the tentative recommended phase 2 dose of 30 mg/kg and higher. Promising efficacy signals were seen in multiple tumor types, including an ORR of 11.8% and DCR of 82.4% in non-small cell lung cancer (NSCLC), and an ORR of 25.0% and DCR of 75.0% in triple-negative breast cancer (TNBC).

CS2009 demonstrated favorable pharmacokinetic and pharmacodynamic profiles, with linear PK and a half-life of 6-8 days supporting every-three-week dosing. Receptor occupancy of PD-1/CTLA-4 on peripheral T cells reached saturation at doses ≥20 mg/kg, and VEGFA was deeply and rapidly reduced across all dose levels, with sustained effects throughout dosing intervals.